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| 5mg |
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| 10mg |
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| Targets |
GSK-3 Inhibitor XIII targets Glycogen Synthase Kinase-3 (GSK-3) as an ATP-competitive inhibitor with a Ki of 24 nM. It also inhibits Aurora A kinase (Ki=58 nM) and Src (Ki=81 nM). By inhibiting GSK-3, it modulates the Wnt/β-catenin pathway, making it a valuable tool in research on cancer, neurodegenerative diseases, and diabetes. The compound also stabilizes a wide array of kinases including AMPKA2, CAMK1D, CAMK2A, ERK1, and VRK3. Its mechanism involves ATP-competitive inhibition at the kinase active site.
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| ln Vitro |
In vitro, GSK-3 Inhibitor XIII is a potent ATP-competitive GSK-3 inhibitor with a Ki of 24 nM. It also inhibits Aurora A kinase (Ki=58 nM) and Src (Ki=81 nM). The compound exhibits significant antiproliferative activity against human COLO205 cells with an IC50 of 1400 nM and against various other human cancer cell lines with IC50 values ranging from 883 nM to 7990 nM. Additionally, it inhibits human recombinant PKR autophosphorylation with an IC50 of 15000 nM. It stabilizes multiple kinases including AMPKA2, CAMK1D, CAMK2A, ERK1, and VRK3.
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| ln Vivo |
In vivo studies of GSK-3 Inhibitor XIII are limited in publicly available literature. As a potent GSK-3 inhibitor, it is expected to modulate the Wnt/β-catenin pathway and influence glycogen metabolism, potentially affecting glucose homeostasis and cellular proliferation. Given its antiproliferative activity against various cancer cell lines in vitro, it may have potential for in vivo investigations of cancer, diabetes, and neurodegenerative diseases. However, specific in vivo efficacy data and detailed animal model studies have not been extensively reported. Further research is needed to establish its in vivo activity profile.
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| Enzyme Assay |
For GSK-3 kinase activity assays, recombinant human GSK-3 enzyme is incubated with appropriate peptide substrates and varying concentrations of GSK-3 Inhibitor XIII in the presence of ATP. Kinase activity is measured by quantifying substrate phosphorylation using radioactive [γ-33P]-ATP or by luminescent ADP-Glo assays. IC50 or Ki values are calculated from dose-response curves. For selectivity profiling, similar assays are performed with a panel of kinases including Aurora A, Src, AMPKA2, CAMK1D, CAMK2A, ERK1, and VRK3. Assays are performed in triplicate with appropriate vehicle controls and reference inhibitors as positive controls.
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| Cell Assay |
For in vitro cellular assays, cancer cell lines such as COLO205 or other human cancer cell lines are cultured in appropriate media under standard conditions (37°C, 5% CO2). GSK-3 Inhibitor XIII is dissolved in DMSO and diluted in culture medium to desired concentrations. Cells are treated with compound for specified durations (typically 48-72 hours). Cell viability and proliferation are assessed using MTT, CCK-8, or ATP-luminescence assays. IC50 values for antiproliferative activity are calculated from dose-response curves. For mechanism studies, downstream signaling markers such as β-catenin and phosphorylated GSK-3 substrates can be analyzed by Western blot. Each concentration is tested in replicate wells with vehicle controls.
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| Animal Protocol |
For in vivo animal studies of GSK-3 Inhibitor XIII, no specific published protocols are available. For general in vivo administration of GSK-3 inhibitors, compounds are typically formulated in suitable vehicles such as 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline and administered via intraperitoneal (i.p.) injection or oral gavage. Dosing regimens vary by study objective. For diabetes models, blood glucose levels may be monitored. For cancer models, tumor growth is monitored. Blood and tissue samples may be collected for pharmacokinetic analysis. All procedures must follow institutional animal care and use committee guidelines.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of GSK-3 Inhibitor XIII are characteristic of a small-molecule kinase inhibitor. The compound has a molecular weight of 301.35, formula C18H15N5, and CAS number 404828-14-4. Purity: 99.95%. Appearance: white to yellow solid. Storage: powder at -20°C for 3 years; in solvent at -80°C for 1 year. Solubility: DMSO 80 mg/mL (265.47 mM) with sonication. In vivo formulation: 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline (3.3 mg/mL). Specific pharmacokinetic parameters such as half-life, clearance, and bioavailability are not extensively reported.
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| Toxicity/Toxicokinetics |
According to available safety information, GSK-3 Inhibitor XIII is intended for research purposes only and is not for human use. Standard laboratory safety precautions should be followed when handling this compound, including the use of appropriate personal protective equipment (gloves, lab coat, safety goggles). The compound should be handled in a well-ventilated area. Avoid dust formation and inhalation. In case of skin contact, wash with plenty of soap and water. In case of eye contact, rinse cautiously with water for several minutes. No clinical toxicity data are available.
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| References |
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| Additional Infomation |
GSK3-XIII belongs to the aromatic amine class of compounds. Its structure is an ammonia molecule, in which two hydrogen atoms are replaced by 5-methylpyrazol-3-yl and 2-phenylquinazoline-4-yl groups, respectively. It is an EC 2.7.11.26 (tau protein kinase) inhibitor. It belongs to the quinazoline class, pyrazole class, secondary amine class, and aromatic amine class of compounds.
GSK-3 Inhibitor XIII is a potent ATP-competitive GSK-3 inhibitor with a Ki of 24 nM. It also inhibits Aurora A kinase (Ki=58 nM) and Src (Ki=81 nM), and stabilizes multiple other kinases. The compound exhibits significant antiproliferative activity against various human cancer cell lines. It is used to study diabetes, obesity, cancer, and neurodegenerative diseases. The compound modulates the Wnt/β-catenin pathway by inhibiting GSK-3. It is for research use only with no clinical development or regulatory approvals reported. |
| Molecular Formula |
C18H15N5
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| Molecular Weight |
301.345
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| Exact Mass |
301.132
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| CAS # |
404828-14-4
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| PubChem CID |
6419766
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| Appearance |
White to off-white solid powder
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| LogP |
4.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
23
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| Complexity |
384
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1NN=C(NC2C3C(=CC=CC=3)N=C(C3=CC=CC=C3)N=2)C=1
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| InChi Key |
JYCUVOXSZBECAY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H15N5/c1-12-11-16(23-22-12)20-18-14-9-5-6-10-15(14)19-17(21-18)13-7-3-2-4-8-13/h2-11H,1H3,(H2,19,20,21,22,23)
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| Chemical Name |
N-(5-methyl-1H-pyrazol-3-yl)-2-phenylquinazolin-4-amine
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (331.84 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.30 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3184 mL | 16.5920 mL | 33.1840 mL | |
| 5 mM | 0.6637 mL | 3.3184 mL | 6.6368 mL | |
| 10 mM | 0.3318 mL | 1.6592 mL | 3.3184 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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